Coronary heart disease continues to be a leading cause of morbidity and mortality in developed countries. It is rapidly assuming similar trends in developing countries also1. It has been predicted that cardiovascular diseases will be the most important cause of mortality in India in year 20152. Hyperlipidemia defined as elevation in serum levels of cholesterol and triglycerides and decrease in HDL cholesterol levels is acknowledged as a major risk factor for coronary heart disease3. Secondary and possible reversible forms of hyperlipidemias include diabetes mellitus, hypertension, hypothyroidism, nephritic syndrome and obstructive liver disease.
Obesity is a complex multifactorial disease that develops from the interaction between genotype and the environment. The understanding of how and why obesity occurs is incomplete, however it involves the integration of social, behavioral, cultural, physiological, metabolic and genetic factors. The presence of overweight, obesity in a patient is of medical concern for several reasons. It increases the risk for several diseases, particularly cardiovascular diseases and diabetes mellitus. According to a expert panel overweight is defined as a body mass index (BMI) of 25 to 29.3 kg/m2, and obesity as BMI greater than or equal to 30 kg/m2. Obesity is commonly accompanied by elevated serum triglycerides. Triglycerides rich lipoproteins may be directly atherogenic, and they are also the most common manifestation of the atherogenic lipoprotein phenotype4. In the presence of obesity, high serum triglycerides are commonly associated with a clustering of metabolic risk factors known as the metabolic syndrome. Thus in obese patients elevated serum triglycerides are a marker for increased cardiovascular risk.
Weight loss drugs approved by the FDA for long term use may be useful as an adjunct to diet and physical activity for patients with a BMI greater than or equal to 30 and without concomitant obesity related risk factors or diseases. The drugs used to promote weight loss have been anorexiants or appetite suppressants. These drugs work by increasing the secretion of dopamine and norepinephrine, or serotonin into the synaptic neural cleft by inhibiting the reuptake of these neurotransmitters into the neuron or by a combination of both mechanisms. Sibutramine inhibits the reuptake of norepinephrine and serotonin, but it also increases the heart rate and the blood pressure. Orlistatis not an appetite suppressant and has a different mechanism of action as it blocks about one third of fat absorption. This also causes side effects that include the decrease in absorption of fat-soluble vitamins, soft stools and anal leakage5.
There is a great interest in weight loss drugs among the consumers. Because of the possibility of serious adverse effects, it is incumbent upon the practitioner to use the drug therapy with a lot of caution.
Gentiana kurroo was used in synergistic combination with other known plant parts or their extracts to form a pharmaceutically effective formulation. Accordingly studies were undertaken to develop a oral formulation containing herbal drugs along with additives for oral ingestion6.7 to treat acute hyperlipidemia.
Details of Each of the Constituent of the Synergistic Composition of the Instant Application
Gentiana kurroo Family: Gentianaceae
Botanical description: A small perennial herb with a stout rhizome bearing decumbent flowering stems, each with 1–4 blue flowers, commonly found in Kashmir and north-western Himalayas, at altitudes of 5,000–11,000 ft. Leaves radical and cauline, the former oblong-lanceolate and tufted, and the latter linear and in paris united at the base in to a tube.
Phytochemistry: Catalpol, its 6′-cinnamoyl, 6-O-cinnamoyl, 6-O-vanilloyl and 6-O-feruloyl derivatives and aucubin isolated from roots and rhizomes. (Rastogi, R. P., Mehrotra, B. N. (1990–1994). Compendium of Indian Medicinal Plants. Vol. V. PID New Delhi. 387.)
Pharmacology: It is reported that the bitter principle increased the gastric secretion diminishing force of the heart beat and reduced the blood pressure. Mild laxative action was found to be due to the presence of cathartic acid. It is reported the diuretic effect of the drug.
Murraya koenigii Family: Rutaceae
Botanical description: A handsome aromatic, more or less decidous shrub or a small tree, up to 6 m. in height and 15–40 cm in diameter, found almost throughout India and the Andaman Islands up to an altitude of 1500 m. Bark dark brown or almost black; leaves imparpinnate: leaflets 9–25, ovate, lanceolate or somewhat rhomboid, irregularly crenate-dentate, acuminate, obtuse or acute, base usually oblique, almost glabrous above, pubscent beneath gland-dotted, strongly aromatic; flowers in terminal corymbose cymes, white, fragrant; berries sub-glucose or ellipsoid, purplish black when ripe, 2-seeded. It is commonly found in forests, often as gregarious under growth. It is much cultivated for its aromatic levesand for ornament throughout India.
Phytochemistry: Isolation and structure of pyranocarbazole alkaloid—grinimbine, mp.176°. Isolation and synthesis of murrayanine (3-formyl-1-methoxycarbazole), mp. 168°, from bark.New alkaloids—mahanimbine , mp. 94°, koenimbine, mp. 194° and koenigicine , mp. 224°—from fruits and leaves. A carbazole carboxylic acid—mukoeic acid, mp. 242°—from stem bark. Curryangine and curryanine isolated and structure of former proposed. Cyclomahanimbine and mahanimbidine isolated from leaves and their structures proposed. Girinimbine, mahanimbine and isomahanimbine isolated from leaves and roots. Structure of murrayacine isolated from leaves and roots confirmed by synthesis. Structures of mahanine, koenine, koenigine, koenidine and koenimbine isolated from leaves. Mahanimbicine and bicyclomahanimbicine isolated. Scopolin isolated from leave. Synthesis of (±)O-methylmahanine. A new carbazole—murrayacinine isolated from stern bark and its structure determined. Structure of murrayazolidine isolated from stem bark, confirmed by synthesis. Structure of curryanine (murrayazolidine) and curryagine (murrayazoline, mahanimbidine) established by synthesis. A new carbazole alkaloid—mukonine isolated and its structure established. Mukonidine isolated and characterized as 2-hydroxy-3-carbomethoxycarbazole. Structure of mahanimboline elucidated. Mahanimbinol isolated from stem wood and its structure determined. Synthesis of murrayacinine. Synthesis of koenigicinc. Structure of new hexacyclic carbazole alkaloid—isomurrayazoline elucidated. Two new carbazole alkaloids—mukoline and mukolidine isolated and their structure determined. Isolation and structure of muconicine from leaves. Mukonal isolated from stem bark and its structure determined. Stem bark afforded 3-(1,1-dimethylallyl) xanthyletin. Koenoline isolated from root bark and its structure elucidated as 1-methoxy-3-hydroxy-methylcarbazole and confirmed by synthesis. Isolation of 2-methoxy-3-methylcarbazole from seeds and its structure elucidation. Another carbazole alkaloid—2-hydroxy-3-methylcarbazole—isolated from roots. Isolation of mahanine from leaves and its 13C-NMR studied. Isolation of a carbazole alkaloid—murrayazolinol from stem bark and its structure determination. Total synthesis of mukonine, murrayanine dnd koenoline. Total seed lipids (4.4%) contained neutral lipids (85.4%), glycolipids (5.1) and phospholipids (9.5%) neutral lipids consisted of triacylglycerols (73.9), free fatty acids (10.2%) and small amount of diacylglycerols, monoacylglycerols and sterols; glycolipids contained steryl glucoside and acylated steryl glucoside; the phospholipids consisted of phosphatidylethanolamine, phosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylcholine. Isolation of two new carbazole alkaloids—isomahanine and murrayanol from fruits and their characterization by X-ray analysis; in addition, mahanimbine, murrayazolidine, girinimbine, koenimbine and mahanine isolated.
Allium sativa Family: Liliaceae
Botanical description: It is a small plant. The leaves are green, slender, flat and elongated. The stem is smooth and solid. The bulbs are composed of several bulhils (cloves), encased in white or pink skin of the parent bulb. The inflorescence is an umbel initially enclosed in a spathe. Garlic has long been cultivated in India as an important spice or condiment crop. It grows under much the same conditions as the onion, except that it favours a richer soil and a higher elevation.
Phytochemistry: The strong smelling juice of the bulbs contain a mixture of aliphatic mono and polysulphides. The chief constituent is allicin, diallyl disulphide oxide. The latter results from spontaneous enzymatic reduction of allin and 5-allylcystine sulphamide. Thio-glycoside, aminioacids, fatty acids, flavonols, vitamins, trace elements, volatile oils etc. have also been demonstrateds.
Pharmacology: Antibacterial and antifungal activity of garlic has been shown, by several investigators, against many common patho-genic organisms. Staphylococcus aureus, Escheiichia coli, Candida albicans, Shigelia sonnei Salmonella typhi. Essential oils of garlic prevented an increase in a —lipoproteins, pre— a lipoproteins occurring after cholesterol-feeding in rabbit. Fibrinolytic activity was also significantly increased. Inhibition of platelet-aggregation in vitro and in vivo has also been demonstrated with garlic. There have been several studies showing the hypoglycaemic activity of garlic and allicin in animals.
Medicinal uses: The therapeutic value of garlic in functional gastro-intestinal disorders as studied in 29 patients. A significant carminative effect, with a relief of nausea, gascolic, flatulence, belching and heaviness was observed. The effects of fried and raw garlic on blood showed an increase in fibrinolytic activity in 20 patients with ischaemic heart disease. A decrease in triglycerides and cholesterol has been observed. Garlic oil drops are put in the ears for infection and earache. Garlic is also used as an antiinfective agent topically and in other intercurrent infections.
Zingiber officinale Family: Zingiberaceae
Botanical description: It is a small plant. The leaves are green, slender, flat and elongated. The stem is smooth and solid. The bulbs are composed of several bulhils (cloves), encased in white or pink skin of the parent bulb. The inflorescence is an umbel initially enclosed in a spathe. Ginger has been under cultivation from times immemorial.
Medicinal uses: The therapeutic value of garlic in functional gastro-intestinal disorders was studied in 29 patients. A significant carminative effect, with a relief of nausea, gascolic, flatulence, belching and heaviness was observed. The effects of fried and raw garlic on blood showed an increase in fibrinolytic activity in 20 patients with ischaemic heart disease. A decrease in triglycerides and cholesterol has been observed. Garlic oil drops are put in the ears for infection and earache. Garlic is also used as an antiinfective agent topically and in other intercurrent infections.
Phytochemistry: The strong smelling juice of the bulbs contain a mixture of aliphatic mono and polysulphildes. The chief constituent is allicin, diallyl disulphide oxide. The latter results from spontaneous enzymatic reduction of allin and 5-allylcystine sulphamide. Thio-glycoside, aminoacids, fatty acids, flavonols, vitamins, trace elements, volatile oils etc. have also been demonstrateds.
Pharmacology: Antibacterial and antifungal activity of garlic has been shown, by several investigators, against many common patho-genic organisms. Staphylococcus aureus, E. coli, Candida albicans, Shigelia sonnei Salmonella typhi. Essential oils of garlic prevented an increase in a —lipoproteins, pre— a lipoproteins occurring after cholesterol-feeding in rabbits. Fibrinolytic activity was also significantly increased. Inhibition of platelet-aggregation in vitro and in vivo has also been demonstrated with garlic. There have been several studies showing the hypoglycaemic activity of garlic and allicin in animals.
Amorphophallus campanulatus Family: Araceae
Botanical description: A tuberous, stout, indigenous herb, 1.0–1.5 m found almost throughout India. Tubers depressed, globose or hemispherical, dark brown out side, pale dull brown, sometimes almost white, with numerous long roots; leaves solitary, tripartite, 30–90 cm broad.
Medicinal uses: The corms are irritant due to the presence of calcium oxalate. It can also be made pickles. The stems can be used as cattle feed. They are rich in nutrients and minerals. They are carminative, aperient and expectorant. The fresh ones are an acrid stimulant and expectorant and increase appetite and taste. They are applied to treat acute rheumatism. They are also used in dysentery, piles and haemorrhoids.
Phytochemistry: It is nutritious and food values compares well with other stablished. It contains proteins, fat, fiber, carbohydrates, starch, oxalic acid and minerals calcium, phosphorus, Iron and vitamin A. Besides these, glucose, galactose and xylose are also present. The presence of an active diastatic enzyme is reported. The corm contains betulinic acid, beta sitosterol, stigmasterol and beta sitosterol palmitate.
Pharmacology: The methanolic extract of the corms showed significant effect on the uterus of the guinea pig. The fermented juice of the petioles is used to cure diarrhea. The seeds are also applied externally as irritant in treating rheumatic swelling.